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Phase 3 Randomized, Placebo-Controlled Study to Assess Safety, Tolerability, and Efficacy of Garetosmab in Patients With Fibrodysplasia Ossificans Progressiva (OPTIMA)

A Study to Assess Safety, Tolerability and Efficacy of Garetosmab Versus Placebo Administered Intravenously (IV) in Adult Participants With Fibrodysplasia Ossificans Progressiva (FOP) (OPTIMA)

Rhee Susan

Regeneron Pharmaceuticals

777 Old Saw Mill River Road, Tarrytown, NY 10591, USA

clinicaltrials@regeneron.com

Rosario Chikako

Parexel International Inc. Regulatory & Access Consulting

Kayabacho Tower, 1-21-2, Shinkawa, Chuo-ku, Tokyo, 104-0033, Japan

+81-80-8929-3137

Clinicaltrial-registration@parexel.com

Not Recruiting

Dec. 20, 2022

Interventional

randomized controlled trial

double blind

placebo control

parallel assignment

treatment purpose

1. Clinical diagnosis of Fibrodysplasia Ossificans Progressiva (FOP) [(based on findings of congenital malformation of the great toes, episodic soft tissue swelling, and/or progressive Heterotopic Ossification (HO)]
2. Confirmation of FOP diagnosis with documentation of Type I activin A receptor (ACVR1) FOP causing mutation
3. FOP disease activity within 1 year of screening visit. FOP disease activity is defined as pain, swelling, stiffness, or other signs and symptoms associated with FOP flare-ups; or worsening of joint function, or radiographic progression of HO lesions (increase in size or number of HO lesions) with/without being associated with flare-up episodes
4. Willing and able to undergo CT imaging procedures and other procedures as defined in the protocol
Other Protocol Defined Inclusion Criteria Apply

1. Cumulative Analog Joint Involvement Scale (CAJIS) score at screening >19
2. Participant has significant concomitant illness or history of significant illness such as but not limited to cardiac, renal, rheumatologic, neurologic, psychiatric, endocrine, metabolic, or lymphatic disease, that in the opinion of the study investigator might confound the results of the study or pose additional risk to the patient by their participation in the study
3. Previous history or diagnosis of cancer
4. Severely impaired renal function defined as estimated glomerular filtration rate <30 milliliter per minute (mL/min)/1.73 m^2 calculated by the Modification of Diet in Renal Disease equation
5. Uncontrolled diabetes defined as hemoglobin A1C (HbA1c) >9% at screening
6. History of poorly controlled hypertension, as defined by:
a. Systolic blood pressure >=180 mm Hg or diastolic blood pressure >=110 mm Hg at the screening visit
b. Systolic blood pressure of 160 mm Hg to 179 mm Hg or diastolic blood pressure of 100 mm Hg to 109 mm Hg at the screening visit, AND a history of end-organ damage (including history of left-ventricular hypertrophy, heart failure, angina, myocardial infarction, stroke, transient ischemic attack, peripheral arterial disease, end-stage renal disease, and moderate-to-advanced retinopathy)
7. Known history of cerebral vascular malformation
8. Cardiovascular conditions such as New York Heart Association class III or IV heart failure, cardiomyopathy, intermittent claudication, myocardial infarction, or acute coronary syndrome within 6 months prior to screening; symptomatic ventricular cardiac arrhythmia
9. History of severe respiratory compromise requiring oxygen, respiratory support (eg, bilevel positive airway pressure [biPAP] or continuous positive airway pressure [CPAP]), or a history of aspiration pneumonia requiring hospitalization
10. Prior use in the past year and concomitant use of bisphosphonates
11. Concurrent participation in another interventional clinical study or a non-interventional study with radiographic measures or invasive procedures (eg, collection of blood or tissue samples).
12. Treatment with another investigational drug, denosumab, imatinib or isotretinoin in the last 30 days or within 5 half-lives of the investigational drug, whichever is longer
13. Pregnant or breastfeeding women
14. Women of childbearing potential (WOCBP) who are unwilling to practice highly effective contraception, as defined in the protocol
15. Male patients with WOCBP partners who are not willing to use condoms with WOCBP partners to prevent potential fetal exposure, as defined in the protocol
Other Protocol Defined Exclusion Criteria Apply

Both

Fibrodysplasia Ossificans Progressiva

Group 1 [High dose Garetosmab]:
Garetosmab is administered by intravenous (IV) administration every 4 weeks (Q4W).
Drug: Garetosmab
-Garetosmab is supplied as a liquid drug product and will be administered IV.
-Other Names: REGN2477

Group 2 [Low dose Garetosmab]:
Garetosmab is administered by IV administration Q4W.
Drug: Garetosmab
-Garetosmab is supplied as a liquid drug product and will be administered IV.
-Other Names: REGN2477

Group 3 [Placebo]:
Placebo to match garetosmab, is supplied as a liquid solution without the monoclonal antibody (or the protein) and is administered IV Q4W.
Drug: Placebo
-Placebo to match garetosmab, is supplied as a liquid solution without the monoclonal antibody (or the protein) and is administered IV.

1. Number of new HO lesions
2. Incidence and severity of treatment-emergent adverse events of special interest (AESIs)

1. Number of clinician-assessed flare-ups
2. Occurrence of new HO lesions
3. Total volume of new HO lesions
4. Occurrence of patient-reported flare-ups: Reported as Yes/No
5. Number of new HO lesions
6. Occurrence of clinician-assessed flare-ups: Reported as Yes/No
7. Number of patient-reported flare-ups
8. Change in joint function assessment by physician using cumulative analog joint involvement scale (CAJIS)
9. Change in pulmonary function as assessed by spirometry
10. Change in disease severity as assessed by the Patient Global Impression of Severity (PGIS)
11. Change in disease severity as assessed by the Patient's Global Impression of Change (PGIC)
12. Change in disease severity as assessed by the Clinician's Global Impression of Change (CGIC)
13. Concentration of total activin A in serum over time
14. Concentrations of garetosmab in serum over time
15. Incidence of anti-drug antibodies (ADA) to garetosmab over time
16. Titer of ADA to garetosmab over time

Oct. 20, 2022

Yes

All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing <Time Frame> When Regeneron has: - received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication or has globally discontinued development of the product for all indications on or after April 2020 and has no plans for future development - made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry) - the legal authority to share the data, and - ensured the ability to protect participant privacy <Access Criteria> Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf <URL> https://vivli.org/

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